XMRV Buzz: Racaniello Retracts/Miller Jumps In/Retrovirologist ‘Superteam’ To Form Rebuttal/Annette, Judy on Nevada Newsmakers

December 23, 2010

Posted by Cort Johnson

Dr. Racaniello Retracts Statement About XMRV and CFS – showing an admirable commitment to the pursuit of the truth Dr Racaniello made an abrupt about face regarding his statement that the four papers were ‘probably the beginning of the end of XMRV and CFS’. His new blog “XMRV and CFS- It’s Not the End’ paints a very different picture andemonstrates just how difficult a subject this is. Dr. Racaniello runs a research lab – he is well versed in this field – yet this is what it took for him to alter his opinion:

“I read the papers over again, and began checking XMRV sequences in Genbank. I also began an email correspondence with authors of three of the four papers, and spoke with my virology colleagues here at Columbia. As a consequence of this additional research I decided that my initial impression of the papers was incorrect, which is evident in my post entitled ‘Is XMRV a laboratory contaminant?”

This is difficult stuff! He does believe that the new papers do highlight the dangers of contamination but they do not imply that the positive results from the WPI’s or other studies were contaminated. He is fully in line with Dr. Coffin, here, who co-authored two of those papers.

“Upon re-reading three of the four Retrovirology papers it became clear to me that they show that identification of XMRV can be fraught with contamination problems, but they do not imply that previously published studies are compromised by these findings. Clearly any new studies done on XMRV should keep in mind the potential for contamination from PCR kits and murine nucleic acids.”

Three of the papers were nothing but warnings; the Hue paper was the most substantial one and the one that bothered him the most but here, again, he was able to find reasons, some of which the WPI mentioned in their rebuttal, why the Hue paper might not apply to the WPI’s findings. He seems to be indicating, oddly enough, that some XMRV isolates appear to be laboratory contaminants while others do not – was an amazing twist in an already very complex field! However, this is a twist that should be able to accounted for one would think – simply by analyzing the different strains (?). Vectors from the MoMLV virus appeared to be used in gene therapy, by the way, which is one reason they might be present in labs. The WPI, however, said the type of mice Hue described have not been used in their labs.

The idea that PCR amplification could itself cause increased variability in 22Rv1 making it look like the ancestor to XMRV indicated just how complex all this is. Willow on the Phoenix Rising Forums has provided a way this could occur.

“I was initially more troubled by the fourth paper by Hue and colleagues. There are four major findings in this paper (gag PCR primers are not specific for XMRV; the virus is present in 5 human tumor cell lines; two XMRV isolates are nearly identical to a virus from the human prostate cell line and also contain an insertion from the murine retrovirus MoMLV; and there is more nucleotide diversity in viral sequences from 22Rv1 cells than in all the patient XMRV sequences). The fact that two XMRV isolates seem to be laboratory contaminants – judged by the presence of MoMLV sequences – was initially unsettling until it became clear that other XMRV isolates do not have this insertion. That leaves the fourth finding – that XMRV from 22Rv1 cells appears ancestral to, and more diverse than, all the human XMRV sequences. I decided that this result was less troublesome than I had originally believed, in part because it is not clear that the differences among the 22Rv1 viruses did not arise during PCR amplification.”

He concluded the blog with an apology and stated that the research on XMRV and CFS must proceed and, in fact, called for it to increase.

My conclusion is that these four papers point out how identification of XMRV from human specimens can be complicated by contamination, but they do not mean that previous studies were compromised. They serve as an important reminder that future experiments to identify XMRV need to be appropriately controlled to ensure that the results are not compromised by contamination.

In other words, these four papers are NOT the beginning of the end of XMRV and CFS. Rather, research on the role of this virus in human disease must proceed, with large, case-controlled epidemiological studies, as suggested by others. I would like to apologize to anyone who was offended, angered, or disappointed in any way by my statement to the Chicago Tribune. It is my goal to educate the public about virology, and clearly I did not do that very well.

There are at least two lessons that you can take away from this incident. First, that I make mistakes, and that I’m willing to admit it. Everyone does, including scientists. Second, if I had difficulties interpreting these papers, how would non-scientists fare?

The Chicago Tribune quickly printed his retraction

Respected Retrovirologist Tackles XMRV/Retrovirology ‘Superteam’ Formed to Rebut Claims – the biggest news of the day, however, was not Dr. Racaniello’s retraction but EcoClimber’s statement on the Phoenix Rising Forums stating that the Retrovirology papers have prompted noted retroviriologist Dr. Dusty Miller at the Fred Hutchinson Cancer Research Institute in Seattle, Washington to dive into his lab to investigate the contamination claims – which he does not believe will pan out and will apparently be part of a XMRV retroviral ‘superteam’ that will rebut the claims in an organized fashion. By suggesting XMRV was a contamination – wherever it appeared – Hue’s paper stepped on a lot of toes. It was Silverman, after all, who discovered XMRV in March of 2006 and since then has published 12 papers on it. Klein has been a co-author of several his papers and, of course, Dr. Ruscetti – who is very well respected in the field, was a co-author of the Science paper.

These researchers may very well be doing lab work to specifically counter the Hue papers findings. Ecoclimber stated

I talked to Dr. Dusty Miller. His lab is currently in the stage in testing and experimenting and gathering the evidence to rebut their claims. He states he can refute their claims. He will be getting together with Ruscetti, Silverman, Klein, Smith and others to post their rebuttal as a group against the negative papers.

Annette Whittemore, Dr. Mikovits on Nevada Newsmakers – meanwhile Dr. Mikovits and Annette Whittemore appeared on Nevada Newsmakers to counter the claims of contamination that have been raised by a rather lazy media. Annette painted ME/CFS in broad terms – it is a complex illness that the WPI believes is infectious, involves many pathogens and affects the neuroimmune system and Dr. Mikovits noted the WPI has had interactions with researchers in countries around the world including Norway, Belgium and Spain. Dr Mikovits asserted that multiple tests are needed to detect XMRV because no single test (ie the PCR results in Retrovirology) is accurate enough. (Dr. Lipkin made a similar point in an email).

Dr. Mikovits noted that they were ‘well aware’ of the potential for contamination to skew the results, which, of course, is doubly true given co-author Dr. Sandra Ruscetti’s background in mouse retroviruses and Dr. Mikovits close connection to the Ruscetti’s. Annette Whittemore stated that the Retrovirology papers ‘do not change their findings’ and that “we are moving forward in a positive way”. She also noted that they were not apprised of the results before they were published – suggesting that the original authors are usually give a bit of lead time to respond to negative papers published regarding their findings. Dr. Mikovits noted that any large discovery is going to lead to ‘a lot of pushback’ because the best science always leads to ‘more questions than answers’ and that’s what has happened. (Has it ever….The XMRV discovery pushed researchers into fields and into digging up questions that they had never asked before.)

When the interviewer asked Dr. Mikovits why researchers have not followed the exact methods of the original paper her reply was very interesting. She said that researchers do what they know how to do well and that they do the advances of the last decade very well but that those kinds of techniques are just not ready to take on a new virus like this. Those new techniques have replaced the old-fashioned method of culturing, which is difficult, expensive and time consuming. (Dr. Mikovits has been saying it’s not about the PCR for months). She said researchers think ‘if we can detect HIV using this method we should be able to detect this virus” but ‘that is just not the case at this point, it is too early in the discovery process”.

Caught in a Time Warp? – This point has confused me because they did use PCR to detect the gag sequence in the original paper and PCR. of course, is described by other commentators as something virtually any lab can do. How does this laymen make sense of all this? Perhaps PCR detection of XMRV is so difficult that just the right techniques are required to find it. It could be that small things, unbeknownst to the research community now, are able to knock XMRV off – and this is in fact what the NCI is looking reportedly at. In that case, until the PCR techniques are perfected then culturing and growing more virus and then studying it – figuring out it’s little secrets – and then developing the correct PCR test would seem to make sense. I am just a laymen – no special expertise here – trying to think through these issues. Sometimes I get it right – sometimes I get it wrong; take everything printed here with that grain of salt!

Unfortunately the PCR test was regarded as the main finding of the Science paper – it was what got the lion’s share of attention, and PCR, as Dr Mikovits pointed out, is what researchers in this field generally do now…. Dr. Lipkin and Dr. Miller and others are wary of PCR as the be-all and end-all of detecting viruses, and they are pursuing other means…

Annette Whittemore noted all the other groups at the NIH, NCI, Cornell and University of Utah that are moving forward. When asked about politics Annette Whittemore noted that these issues are money intensive with a lot of stakeholders and some politics is inevitable….When XMRV turns out its going to cost some stakeholders a lot of money (and, of course, make money for some others). This is a long interview and I’m exhausted but it is a good interview. Dr. Mikovits and Annette Whittemore and quite poised and acquit themselves and the organization well, IMHO.

2 comments

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Greg January 14, 2011 at 2:42 am

Dr Dusty Miller at times also states that XMRV will not pan out.

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Cort January 19, 2011 at 5:07 pm

I’ve talked with Dusty Miller and read what he’s written; my understanding from is that he’s right in the middle – he knows and respects Dr. Silverman and the Ruscetti’s – he’s in that generation – and he is also cognizant of the problems finding the virus.

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